A pain signal arising from organ damage or disease is transmitted to the central nervous system where it generates the sensation of pain. The magnitude of the pain stimulus is regulated by a system receptors nociceptive and anti-nociceptive located on neuronal cell membranes. Tachykinin receptors located on neurons of the peripheral and central nervous systems constitute a significant component of nociceptive receptors and play a leading role in the transmission of pain signals. Endogenous opioid peptides are a natural factor responsible for mitigating the pain signal as through the activation of anti-nociceptive receptors. Opioid receptors are also activated through the administration of opioid analgesics such as morphine or phentanyl. Unfortunately, the administration of analgesics available to date causes a series of undesirable side-effects, such as tolerance and drug dependency. The use of peptide analogues of natural opioid peptides with the general formula shown in FIG. 1 makes it possible to decrease tolerance and drug dependence. According to results of experiments on animals presented at the International Narcotic Research Conference 1989 and described in post-conference materials, B. S. Silbert, A. W. Lipkowski, D. B. Carr, S. K. Szyfelbein, P. F. Osgood, in the chapter “Peptides as potential nociceptive drugs.”, pp. 485-488 of “Procc. Int. Narc. Res. Conf.'89”, edited by R. Quirion, Alan R. Liss Inc, New York, 1990, as well as D. Kosson, I. Maszczynska Bonney, D. B. Carr, E. Mayzner-Zawadzka, A. W. Lipkowski, in Antinociceptive properties of biphalin after intrathecal application in rats: a reevaluation. Pharmacological Report. Vol. 57, pp. 545-549, 2005, an opioid peptide with the common name biphalin exhibits significant analgesic activity. This compound exhibits much lesser habit-forming activity, as described in M. Yamazaki, T. Suzuki, M. Narita, A. W. Lipkowski, “The opioid peptide analogue biphalin induces less physical dependence than morphine”, Life Science, Vol. 69, pp. 1023-1028, 2001.
Chemically, biphalin is a dimer of two tetrapeptide opioid pharmacophores. Studies on the relationship between biological activity and biphalin structure show that one of the tetrapeptide fragments may be substituted with a peptide or non-peptide lipophilic component without any significant changes in its affinity for opioid receptors, as described in A. W. Lipkowski, A. Misicka, P. Davis, D. Stropova, J. Janders, M. Lachwa, F. Porreca, H. I. Yamamura, V. J. Hruby, in “Biological activity of fragments and analogues of the potent dimeric opioid peptide, biphalin.”, Bioorganic and Medicinal Chemistry Letters, Vol. 9, pp. 2763-2766, 1999. As a result of substituting one of the tetrapeptide fragments of biphalin with benzoxycarbonyl-L-tryptophan, a compound was produced with affinity for opioid receptors comparable to biphalin, with concurrent activity as a weak tachykinin receptor antagonist. As a result, a compound with strong analgesic properties against inflammatory pain was obtained, as described by I. Maszczynska Bonney, S. E. Foran, J. E. Marchand, A. W. Lipkowski, D. B. Carr in “Spinal antinociceptive effects of AA501, a novel chimeric peptide with opioid receptor agonist and tachykinin receptor antagonist moieties”, European Journal of Pharmacology, Vol. 488, pp. 91-99, 2004.
Citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.